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Imipramine Inhibits A-type Delayed Rectifier and ATP-Sensitive $K^{+}$ Currents Independent of G-Protein and Protein Kinase C in Murine Proximal Colonic Myocytes  

Choi, Seok (Department of Physiology, College of Medicine, Chosun University)
Parajuli, Shankar Prasad (Department of Physiology, College of Medicine, Chosun University)
Lim, Geon-Han (Department of Neurology, College of Medicine, Chosun University)
Kim, Jin-Ho (Department of Neurology, College of Medicine, Chosun University)
Yeum, Cheol-Ho (Department of Physiology, College of Medicine, Chosun University)
Yoon, Pyung-Jin (Department of Physiology, College of Medicine, Chosun University)
Jun, Jae-Yeoul (Department of Physiology, College of Medicine, Chosun University)
Publication Information
Archives of Pharmacal Research / v.29, no.11, 2006 , pp. 998-1005 More about this Journal
Abstract
The effects of imipramine on A-type delayed rectifier $K^{+}$ currents and ATP-sensitive $K^{+}\;(K_{ATP)$ currents were studied in isolated murine proximal colonic myocytes using the whole-cell patch-clamp technique. Depolarizing test pulses between-80 mV and +30 mV with 10 mV increments from the holding potential of-80 mV activated voltage-dependent outward $K^{+}$ currents that peaked within 50 ms followed by slow decreasing sustained currents. Early peak currents were inhibited by the application of 4-aminopyridine, whereas sustained currents were inhibited by the application of TEA. The peak amplitude of A-type delayed rectifier $K^{+}$ currents was reduced by external application of imipramine. The half-inactivation potential and the half-recovery time of A-type delayed rectifier $K^{+}$ currents were not changed by imipramine. With 0.1 mM ATP and 140 mM $K^{+}$ in the pipette and 90 mM $K^{+}$ in the bath solution and a holding potential of -80 mV, pinacidil activated inward currents; this effect was blocked by glibenclamide. Imipramine also inhibited $K_{ATP}$ currents. The inhibitory effects of imipramine in A-type delayed rectifier $K^{+}$ currents and $K_{ATP}$ currents were not changed by guanosine 5-O-(2-thiodiphosphate) ($GDP{\beta}S$) and chelerythrine, a protein kinase C inhibitor. These results suggest that imipramine inhibits A-type delayed rectifier $K^{+}$ currents and $K_{ATP}$ currents in a manner independent of G-protein and protein kinase C.
Keywords
A-type delayed rectifier $K^{+}$ currents; ATP-sensitive $K^{+}$ currents, Imipramine, Colonic myocytes;
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